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What Determines Liver Stiffness?

Measured liver stiffness reflects the mechanical state of the liver at the time of measurement, not fibrosis alone.

Our experimental and clinical studies demonstrated several rapidly reversible determinants of stiffness. Extrahepatic cholestasis increases stiffness through biliary pressure; central venous congestion can produce values in the cirrhotic range; and increased arterial pressure can raise stiffness even when venous pressure is unchanged. Inflammation adds a further dynamic component.

These observations explain why a single high value should not automatically be equated with advanced fibrosis. Clinical interpretation requires the parallel assessment of cholestasis, congestion, inflammation and other infiltrative or hemodynamic conditions.

Matrix deposition and pressure-related mechanisms contribute independently to measured liver stiffness.

Clinical conditions that may increase liver stiffness independent of fibrosis.

Selected publications

• Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Millonig G et al. Hepatology. 2008;48(5):1718–1723.
• Liver stiffness is directly influenced by central venous pressure. Millonig G et al. J Hepatol. 2010;52(2):206–210.
• Arterial pressure suffices to increase liver stiffness. Piecha F et al. Am J Physiol Gastrointest Liver Physiol. 2016;311(5):G945–G953.
• Liver stiffness: a novel parameter for the diagnosis of liver disease. Mueller S, Sandrin L. Hepat Med. 2010;2:49–67.